The Influence of OLR1 and PCSK9 Gene Polymorphisms on Ischemic Stroke: Evidence from a Meta-Analysis

Abstract

Both OLR1 and PCSK9 genes are associated with atherosclerosis, cardiovascular disease and ischemic stroke. The overall prevalence of PCSK9 rs505151 and OLR1 rs11053646 variants in ischemic stroke were 0.005 and 0.116, respectively. However, to date, association between these polymorphisms and ischemic stroke remains inconclusive. Therefore, this first meta-analysis was carried out to clarify the presumed influence of these polymorphisms on ischemic stroke. All eligible case-control and cohort studies that met the search terms were retrieved in multiple databases. Demographic and genotyping data were extracted from each study, and the meta-analysis was performed using RevMan 5.3 and Metafor R 3.2.1. The pooled odd ratios (ORs) and 95% confidence intervals (CIs) were calculated using both fixed- and random-effect models. Seven case-control studies encompassing 1897 cases and 2119 controls were critically evaluated. Pooled results from the genetic models indicated that OLR1 rs11053646 dominant (OR = 1.33, 95% CI:1.11–1.58) and co-dominant models (OR = 1.24, 95% CI:1.02–1.51) were significantly associated with ischemic stroke. For the PCSK9 rs505151 polymorphism, the OR of co-dominant model (OR = 1.36, 95% CI:1.01–1.58) was found to be higher among ischemic stroke patients. In conclusion, the current meta-analysis highlighted that variant allele of OLR1 rs11053646 G > C and PCSK9 rs505151 A > G may contribute to the susceptibility risk of ischemic stroke.

Upregulation of OLR1 and IL17A genes and their association with blood glucose and lipid levels in femoropopliteal artery disease

“…In a recent meta-analysis of seven case-control studies, it was observed that OLR1 SNP rs11053646 dominant and co-dominant models were significantly associated with ischemic stroke (28). In the present study, OLR1 SNP rs11053646 recessive and co-dominant models were not significantly associated with the risk of FP artery disease.…”

The effect of APOE, CETP, and PCSK9 polymorphisms on simvastatin response in Thai hypercholesterolemic patients

“…Gain‐of‐function and loss‐of‐function PCSK9 mutations are associated with hypercholesterolemia and hypocholesterolemia, respectively . Moreover, PCSK9 polymorphisms have been reported to be associated with LDL‐C levels, LDL‐C lowering response to statins, and risk of premature CVD and ischemic stroke …”

Large-scale phenome-wide association study of PCSK9 loss-of-function variants demonstrates protection against ischemic stroke

“…10,21,23,32 Like studies on statin effects, several clinical trials and genetic studies have explored the effects of PCSK9 inhibitors on lipid levels, coronary heart disease, mortality, stroke, T2D and cognitive effects; these studies are often hampered by small sample sizes and offer conflicting evidence that can impact our understanding of new indications, safety considerations, and side effects. 12,33–35 Hence, we developed a list of 11 hypothesis-driven phenotypes with careful definitions to evaluate the evidence of association of PCSK9 variants with phenotypes of interest in concurrent literature. 21,24,26,27…”

“…A handful of small studies have shown suggestive evidence for the association between PCSK9 variants and ischemic stroke. 12,35,38 However, larger studies have offered conflicting evidence. Two recent meta-analyses using genetic data 39 and randomized clinical data 40 showed no association between PCSK9 inhibition and ischemic stroke.…”